Cancer is currently the leading cause of death. However, despite extensive research having been conducted on a wide range of treatment methods, such as surgical intervention or radiotherapy, cancer has yet to be overcome, and considerable amounts of funding and time are being devoted to cancer research even now.
In particular, chemotherapy is one of the major forms of treatment, and numerous anticancer drugs have been researched and developed. For example, various anticancer drugs are known, including alkylating agents, platinum preparations, metabolic antagonists and plant alkaloids.
Gemcitabine hydrochloride (Gemzar®) is a fluorinated pyrmidine-based anticancer drug that is classified as a metabolic antagonist, and as a result of being metabolized in cells, is converted to active nucleotides in the form a diphosphate and triphosphate that are known to demonstrate cytocidal action by directly or indirectly inhibiting DNA synthesis. Gemcitabine hydrochloride has been approved in Japan for use in pancreatic cancer, non-small-cell lung cancer and biliary tract cancer, and has been approved overseas for use in breast cancer, urinary bladder cancer, ovarian cancer and cervical cancer.
On the other hand, extensive research has recently been conducted on drug delivery systems (DDS), which constitute a technology for delivering a drug to be administered to a specific site where the drug is to act in the body while controlling the duration of administration and dosage of the drug for the purpose of enhancing efficacy and reducing adverse side effects. Specific examples of DDS means that are used include methods using liposomes, emulsions or nanoparticles as drug carriers, methods in which drugs are enclosed in polymeric carriers such as high molecular weight synthetic polymer micelles, and methods in which drugs are covalently bonded to synthetic polymers or natural polysaccharides.
Among these methods, WO 02/262414A1 discloses a coordination compound in which cisplatin is coordination-bonded to a carboxy anion of a block copolymer composed of poly(ethylene glycol) and poly(glutamic acid). This coordination compound forms polymer micelles in an aqueous medium, has been reported to be able to reduce nephrotoxicity attributable to cisplatin in animal studies (Br. J. Cancer, 19, 93(6), 678-87 (2005)), and is currently at the stage of clinical studies.
However, despite research and development of various anticancer drugs, cancer has yet to be overcome, and since there are limitations on dosage due to potent toxicity on normal cells in the case of treatment using a single anticancer drug, and from the viewpoint of response rate and adverse side effects, current treatment cannot be said to be adequate with the exception of some cancers. Thus, numerous attempts have been made using concomitant therapy combining various anticancer drugs. For example, A. M. Bergman, et al., Clin. Cancer Res., 2, 521-530 (1996) reports concomitant effects of gemcitabine hydrochloride and cisplatin.